Protein: P12956

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
P12956 (Uniprot) XRCC6_HUMAN XRCC6 X-ray repair cross-complementing protein 6 human Yes
Uniprot: Single-stranded DNA-dependent ATP-dependent helicase. Has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. Binding to DNA may be mediated by XRCC6. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The XRCC5/6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold. The XRCC5/6 dimer is probably involved in stabilizing broken DNA ends and bringing them together. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. Required for osteocalcin gene expression. Probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks. 5'-dRP lyase activity allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined. The XRCC5/6 dimer together with APEX1 acts as a negative regulator of transcription. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway. more..
Dissimilar Functions Manual Curation

Function 1: DNA repair (NHEJ).

Function 2: Telomere maintainance in association with NARG1, the Ku p70/p86 dimer binds to the osteocalcin promoter and activates osteocalcin expression.

Publications (PMID): 12145306

Biological Processes
Module ID (MoonGO) GO ID (BP) GO Name
51 GO:0060255 regulation of macromolecule metabolic process
107 GO:0016070 RNA metabolic process
107 GO:0044267 cellular protein metabolic process
107 GO:0034654 nucleobase-containing compound biosynthetic process
107 GO:2000112 regulation of cellular macromolecule biosynthetic process
107 GO:0010468 regulation of gene expression
107 GO:0019219 regulation of nucleobase-containing compound metabolic process
107 GO:0007165 signal transduction
123 GO:0006464 cellular protein modification process
123 GO:0006355 regulation of transcription, DNA-templated
173 GO:0034645 cellular macromolecule biosynthetic process
173 GO:0006464 cellular protein modification process
173 GO:0010467 gene expression
173 GO:0035556 intracellular signal transduction
173 GO:0090304 nucleic acid metabolic process
173 GO:0016310 phosphorylation
173 GO:0031325 positive regulation of cellular metabolic process
173 GO:0010604 positive regulation of macromolecule metabolic process
173 GO:0051173 positive regulation of nitrogen compound metabolic process
173 GO:0031326 regulation of cellular biosynthetic process
173 GO:0019219 regulation of nucleobase-containing compound metabolic process
181 GO:0044267 cellular protein metabolic process
181 GO:0010467 gene expression
181 GO:0009059 macromolecule biosynthetic process
181 GO:0090304 nucleic acid metabolic process
181 GO:0060255 regulation of macromolecule metabolic process
181 GO:0007165 signal transduction
217 GO:0060255 regulation of macromolecule metabolic process
217 GO:0007165 signal transduction
220 GO:0060255 regulation of macromolecule metabolic process
239 GO:0006139 nucleobase-containing compound metabolic process
266 GO:0034645 cellular macromolecule biosynthetic process
266 GO:0044271 cellular nitrogen compound biosynthetic process
266 GO:0006464 cellular protein modification process
266 GO:0070887 cellular response to chemical stimulus
266 GO:0032270 positive regulation of cellular protein metabolic process
266 GO:0048584 positive regulation of response to stimulus
266 GO:0006508 proteolysis
266 GO:0050790 regulation of catalytic activity
266 GO:0031326 regulation of cellular biosynthetic process
266 GO:0010468 regulation of gene expression
266 GO:2000026 regulation of multicellular organismal development
266 GO:0019219 regulation of nucleobase-containing compound metabolic process
266 GO:0009966 regulation of signal transduction
273 GO:0034645 cellular macromolecule biosynthetic process
273 GO:0044271 cellular nitrogen compound biosynthetic process
273 GO:0006464 cellular protein modification process
273 GO:0051252 regulation of RNA metabolic process
273 GO:0010468 regulation of gene expression
286 GO:0034645 cellular macromolecule biosynthetic process
286 GO:0090304 nucleic acid metabolic process
286 GO:0034654 nucleobase-containing compound biosynthetic process
286 GO:0010468 regulation of gene expression
305 GO:0060255 regulation of macromolecule metabolic process
404 GO:0044267 cellular protein metabolic process
404 GO:0007165 signal transduction
428 GO:0044267 cellular protein metabolic process
428 GO:0090304 nucleic acid metabolic process
428 GO:0060255 regulation of macromolecule metabolic process
484 GO:0006139 nucleobase-containing compound metabolic process
484 GO:1901362 organic cyclic compound biosynthetic process
484 GO:0019538 protein metabolic process
484 GO:0060255 regulation of macromolecule metabolic process
484 GO:0007165 signal transduction
555 GO:0006464 cellular protein modification process
555 GO:0060255 regulation of macromolecule metabolic process
555 GO:0007165 signal transduction
573 GO:0006464 cellular protein modification process
573 GO:0006139 nucleobase-containing compound metabolic process
573 GO:0060255 regulation of macromolecule metabolic process
573 GO:0007165 signal transduction
621 GO:0006355 regulation of transcription, DNA-templated
819 GO:0010628 positive regulation of gene expression
819 GO:0019538 protein metabolic process
819 GO:0006355 regulation of transcription, DNA-templated
838 GO:0031325 positive regulation of cellular metabolic process
838 GO:0010628 positive regulation of gene expression
838 GO:0051173 positive regulation of nitrogen compound metabolic process
838 GO:0006357 regulation of transcription from RNA polymerase II promoter
Cellular Components
Module ID (MoonGO) GO ID (CC) GO Name
39 GO:0043232 intracellular non-membrane-bounded organelle
51 GO:0005634 nucleus
101 GO:0005829 cytosol
101 GO:0043232 intracellular non-membrane-bounded organelle
107 GO:0005829 cytosol
107 GO:0005654 nucleoplasm
123 GO:0043232 intracellular non-membrane-bounded organelle
123 GO:0005654 nucleoplasm
173 GO:0005654 nucleoplasm
181 GO:0005829 cytosol
181 GO:0005654 nucleoplasm
217 GO:0005829 cytosol
217 GO:0043232 intracellular non-membrane-bounded organelle
220 GO:0005634 nucleus
239 GO:0043232 intracellular non-membrane-bounded organelle
239 GO:0031981 nuclear lumen
266 GO:0031410 cytoplasmic vesicle
266 GO:0012505 endomembrane system
266 GO:0005576 extracellular region
266 GO:0070013 intracellular organelle lumen
266 GO:0005634 nucleus
266 GO:0005886 plasma membrane
273 GO:0043232 intracellular non-membrane-bounded organelle
273 GO:0005654 nucleoplasm
286 GO:0044428 nuclear part
291 GO:0043232 intracellular non-membrane-bounded organelle
291 GO:0005634 nucleus
305 GO:0005634 nucleus
404 GO:0005829 cytosol
404 GO:0012505 endomembrane system
404 GO:0031982 vesicle
428 GO:0043232 intracellular non-membrane-bounded organelle
428 GO:0031981 nuclear lumen
447 GO:0005829 cytosol
447 GO:0043232 intracellular non-membrane-bounded organelle
447 GO:0005634 nucleus
466 GO:0005829 cytosol
484 GO:0070013 intracellular organelle lumen
484 GO:0005634 nucleus
555 GO:0005634 nucleus
573 GO:0005829 cytosol
573 GO:0012505 endomembrane system
573 GO:0070013 intracellular organelle lumen
573 GO:0044428 nuclear part
573 GO:0031982 vesicle
621 GO:0005634 nucleus
666 GO:0016021 integral component of membrane
819 GO:0098588 bounding membrane of organelle
819 GO:0005829 cytosol
819 GO:0012505 endomembrane system
819 GO:0005576 extracellular region
819 GO:0005634 nucleus
819 GO:0031982 vesicle
838 GO:0005654 nucleoplasm
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0000723 telomere maintenance TAS
GO:0002218 activation of innate immune response IDA
GO:0006266 DNA ligation TAS
GO:0006303 double-strand break repair via nonhomologous end joining TAS
GO:0006310 DNA recombination IEA
GO:0006351 transcription, DNA-templated IEA
GO:0007420 brain development IEA
GO:0032481 positive regulation of type I interferon production TAS
GO:0032508 DNA duplex unwinding IEA
GO:0043312 neutrophil degranulation TAS
GO:0045087 innate immune response IEA
GO:0045860 positive regulation of protein kinase activity IDA
GO:0045892 negative regulation of transcription, DNA-templated IMP
GO:0045893 positive regulation of transcription, DNA-templated IMP
GO:0045944 positive regulation of transcription from RNA polymerase II promoter IMP
GO:0048660 regulation of smooth muscle cell proliferation IMP
GO:0051290 protein heterotetramerization IDA
GO:0071475 cellular hyperosmotic salinity response IEA
GO:0071480 cellular response to gamma radiation IDA
GO:0071481 cellular response to X-ray IEA
GO:0075713 establishment of integrated proviral latency TAS
GO:0097680 double-strand break repair via classical nonhomologous end joining IDA
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0000783 nuclear telomere cap complex TAS
GO:0000784 nuclear chromosome, telomeric region IDA
GO:0005576 extracellular region TAS
GO:0005634 nucleus TAS
GO:0005654 nucleoplasm TAS
GO:0005667 transcription factor complex IDA
GO:0005730 nucleolus IDA
GO:0005829 cytosol TAS
GO:0016020 membrane IDA
GO:0032993 protein-DNA complex IDA
GO:0034774 secretory granule lumen TAS
GO:0043234 protein complex IDA
GO:0043564 Ku70:Ku80 complex IDA
GO:0070419 nonhomologous end joining complex IDA
GO:1904813 ficolin-1-rich granule lumen TAS
GO ID 1 Component 1 GO ID 2 Component 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0005576 extracellular region GO:0005634 nucleus 4.48e-91 1.28e-107
GO:0005576 extracellular region GO:0005654 nucleoplasm 6.62e-72 7.68e-98
GO:0005576 extracellular region GO:0005667 transcription factor complex 2.39e-24 8.05e-200
GO:0005576 extracellular region GO:0005730 nucleolus 6.04e-15 4.85e-05
GO:0005634 nucleus GO:0016020 membrane 0.00e+00 4.39e-236
GO:0005654 nucleoplasm GO:0016020 membrane 5.76e-255 1.32e-206
GO:0005667 transcription factor complex GO:0016020 membrane 1.61e-58 1.75e-266
GO:0005730 nucleolus GO:0016020 membrane 8.89e-46 1.83e-10
GO:0016020 membrane GO:0032993 protein-DNA complex 3.22e-21 3.33e-35
Interactor Also a MoonDB EMF protein
COIL_HUMAN No
CTBP2_HUMAN No
ILVBL_HUMAN No
1433Z_HUMAN Yes: P63104 (MoonDB)
A0A0G2JPK4_HUMAN No
ABCD4_HUMAN No
ACD_HUMAN Yes: Q96AP0 (MoonDB)
ADCY7_HUMAN No
ANXA1_HUMAN No
AP2C_HUMAN No
APLF_HUMAN No
ARAP1_HUMAN No
ATP23_HUMAN No
BTG1_HUMAN No
C560_HUMAN No
CAN11_HUMAN No
CBP_HUMAN No
CBX5_HUMAN Yes: P45973 (MoonDB)
CCNA1_HUMAN No
CDCA5_HUMAN No
CENPU_HUMAN No
CKLF6_HUMAN No
CLH1_HUMAN Yes: Q00610 (MoonDB)
CLUS_HUMAN No
COPB_HUMAN No
DYSF_HUMAN No
EFNA1_HUMAN No
EID1_HUMAN No
EP300_HUMAN Yes: Q09472 (MoonDB)
EPS8_HUMAN No
FMNL1_HUMAN No
G3ST4_HUMAN No
GATA_HUMAN No
GOLP3_HUMAN No
GSE1_HUMAN No
HD_HUMAN Yes: P42858 (MoonDB)
HERP1_HUMAN No
HMGA1_HUMAN No
HMGA2_HUMAN No
HXC4_HUMAN No
JUPI2_HUMAN No
K0408_HUMAN No
KAP0_HUMAN No
KAT2A_HUMAN No
M4K2_HUMAN No
MP2K5_HUMAN No
MRE11_HUMAN No
MSH6_HUMAN No
NCF4_HUMAN No
NCPR_HUMAN No
NH2L1_HUMAN No
NIT1_HUMAN No
NOTC1_HUMAN No
NSMA2_HUMAN No
PA1B3_HUMAN No
PAEP_HUMAN No
PARP1_HUMAN No
PCNA_HUMAN Yes: P12004 (MoonDB)
PDK1_HUMAN No
PDPK1_HUMAN Yes: O15530 (MoonDB)
PECA1_HUMAN No
PFD3_HUMAN No
PGAM1_HUMAN No
PLRKT_HUMAN No
PNRC2_HUMAN No
PO2F2_HUMAN No
PPM1G_HUMAN No
PRKDC_HUMAN No
PTTG1_HUMAN No
RASA1_HUMAN No
RBBP4_HUMAN No
RGS2_HUMAN No
RLA1_HUMAN No
RRAS2_HUMAN No
RS10_HUMAN No
SEP15_HUMAN No
SKIL_HUMAN No
SMAD3_HUMAN Yes: P84022 (MoonDB)
SMAD7_HUMAN No
SNTA1_HUMAN No
SPB9_HUMAN No
SPRC_HUMAN No
TADA3_HUMAN No
TBCD_HUMAN No
TCPG_HUMAN No
TE2IP_HUMAN No
TERF2_HUMAN No
TKN1_HUMAN No
VATE1_HUMAN No
VAV_HUMAN No
WRN_HUMAN No
XRCC5_HUMAN Yes: P13010 (MoonDB)
Z512B_HUMAN No
PMID Article Title
1537839 Identification of proteins binding to interferon-inducible transcriptional enhancers in hematopoietic cells.
1608402 Nucleotide sequence and genomic structure analyses of the p70 subunit of the human Ku autoantigen: evidence for a family of genes encoding Ku (p70)-related polypeptides.
2466842 Molecular cloning of cDNA encoding the p70 (Ku) lupus autoantigen.
2917966 Cloning and characterization of a cDNA that encodes a 70-kDa novel human thyroid autoantigen.
7882982 Purification of the sequence-specific transcription factor CTCBF, involved in the control of human collagen IV genes: subunits with homology to Ku antigen.
7957065 Human DNA helicase II: a novel DNA unwinding enzyme identified as the Ku autoantigen.
8605992 Non-histone protein 1 (NHP1) is a member of the Ku protein family which is upregulated in differentiating mouse myoblasts and human promyelocytes.
8621488 The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium.
9362500 Double-strand break repair by Ku70 requires heterodimerization with Ku80 and DNA binding functions.
9742108 Productive and nonproductive complexes of Ku and DNA-dependent protein kinase at DNA termini.
10026262 DNA-dependent protein kinase phosphorylation sites in Ku 70/80 heterodimer.
10219089 Isolation of Ku70-binding proteins (KUBs).
10377944 Ku, a DNA repair protein with multiple cellular functions?
10591208 The DNA sequence of human chromosome 22.
11457852 The three-dimensional structure of the C-terminal DNA-binding domain of human Ku70.
11493912 Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair.
12145306 Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex.
12509254 Defining interactions between DNA-PK and ligase IV/XRCC4.
12547193 Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment.
14702039 Complete sequencing and characterization of 21,243 full-length human cDNAs.
15075319 Positive and negative modulation of the transcriptional activity of the ETS factor ESE-1 through interaction with p300, CREB-binding protein, and Ku 70/86.
15489334 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
18669648 A quantitative atlas of mitotic phosphorylation.
19413330 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19608861 Lysine acetylation targets protein complexes and co-regulates major cellular functions.
19690332 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
20068231 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
20383123 Ku is a 5'-dRP/AP lyase that excises nucleotide damage near broken ends.
20493174 55K isoform of CDK9 associates with Ku70 and is involved in DNA repair.
21269460 Initial characterization of the human central proteome.
21406692 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
22223895 Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.
22442688 Deformed epidermal autoregulatory factor-1 (DEAF1) interacts with the Ku70 subunit of the DNA-dependent protein kinase complex.
23186163 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
24275569 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24610814 A human short open reading frame (sORF)-encoded polypeptide that stimulates DNA end joining.
25218447 Uncovering global SUMOylation signaling networks in a site-specific manner.
25574025 DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair.
25670504 Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway.
25852083 DNA-dependent protein kinase (DNA-PK) permits vascular smooth muscle cell proliferation through phosphorylation of the orphan nuclear receptor NOR1.
25941166 XLS (c9orf142) is a new component of mammalian DNA double-stranded break repair.
25944712 N-terminome analysis of the human mitochondrial proteome.
26359349 Heat shock factor 1, an inhibitor of non-homologous end joining repair.
28112733 Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.
28712728 HEXIM1 and NEAT1 Long non-coding RNA form a multi-subunit complex that regulates DNA-mediated innate immune response.
28959974 Regulation of DNA repair pathway choice in S and G2 phases by the NHEJ inhibitor CYREN.
No results found.
Domain Name Domain ID Source
A30894 A30299 PIR
SAP_dom IPR003034 InterPro
Ku_C IPR005160 InterPro
Ku_N IPR005161 InterPro
Ku70/Ku80_beta-barrel_dom IPR006164 InterPro
Ku70 IPR006165 InterPro
SPOC-like_C_dom_sf IPR016194 InterPro
Ku70_bridge/pillars_dom_sf IPR027388 InterPro
SAP_dom_sf IPR036361 InterPro
vWFA_dom_sf IPR036465 InterPro
SAP PF02037 Pfam
Ku PF02735 Pfam
Ku_C PF03730 Pfam
Ku_N PF03731 Pfam
Ku70 PIRSF003033 PIRSF
SAP PS50800 PROSITE
PTHR12604:SF2 PTHR12604:SF2 PANTHER
SAP SM00513 SMART
Ku78 SM00559 SMART
SSF100939 SSF100939 SUPFAM
SSF53300 SSF53300 SUPFAM
SSF68906 SSF68906 SUPFAM
ku70 TIGR00578 TIGRFAMs